Main methods used for cancer treatment include surgery, anticancer chemotherapy, radiotherapy, etc. Among them, surgery and radiotherapy are local therapies showing effects only in excised or irradiated areas, and anticancer chemotherapy is a systemic therapy showing effects throughout the body. Most cancers occur locally and metastasize systemically. In many cases, cancers are diagnosed after metastasis unless diagnosed very early. Accordingly, cancers often recur even after an effective local therapy. Thus, for most cancer treatment, local therapy is used together with anticancer chemotherapy to improve effectiveness against systemically spread cancer.
Administration of anticancer therapy drugs is important for removing either a very small cancer tissue difficult to observe visually after surgical removal of cancer sites, or cancer cells metastasized from a primary site to other tissues. However, when a cancer is resistant to a specific anticancer drug, or a specific anticancer drug is administered long term cancer cells may acquire drug resistance and thus anticancer effects may not be sufficient. Known anticancer drugs to which cancer cells can acquire resistance mainly include hydrophilic and amphiphilic drugs, for example, taxane, vinca alkaloid drugs (vinorelbine, vincristine, and vinblastine), anthracycline drugs (doxorubicin, daunorubicin, and epirubicin), epidophyllotoxin (etoposide, and teniposide), antimetabolites (methorexate, fluorouracil, cytosar, 5-azacytosine, 6-mercaptopurine, and gemcitabine), topotecan, dactinomycin, mitomycin, etc. The problem that cancer cells acquire resistance to anticancer drugs in anticancer therapy has long been a great obstacle in treating tumors.
Various studies have been conducted to resolve this obstacle. For example, Korean Patent Application Publication No. 2011-88771 discloses a method of treating cancer resistant to cetuximab or gefitinib by administering a PI3K/Akt inhibitor in combination with cetuximab or gefitinib. Korean Patent Application Publication No. 2011-139397 discloses a method of preventing or treating anticancer drug-resistant cancers using 5,6-benzoflavone compounds, and WO 2011/031842 discloses a method of using N-(4-((3-(2-amino-4-pyrimidinyl)-2-pyridinyl)oxy)phenyl)-4-(4-methyl-2-thienyl)-1-phthalazinamine or a pharmaceutically acceptable salt thereof, to treat solid tumors that have become resistant to treatment with chemotherapeutic agents. In addition, WO 2011/031890 discloses a method of treating drug-resistant cancers by administering a therapeutically effective amount of sodium meta-arsenite to a subject in need thereof. However, such methods for treating drug-resistant cancers have a shortcoming that they can be applied only to patients satisfying specific conditions, and thus cannot be effectively applied to treat general drug-resistant cancers.
At present, to increase the treatment rate for cancers, there is a need to expand radical surgery by early diagnosis and develop a method of effectively using anticancer chemotherapy for patients who cannot undergo surgery or patients who have a high risk of recurrence after surgery. In order to develop the therapeutic method, the mechanism of cancer cells' resistance to anticancer drugs should be elucidated, and based on the finding, a method of overcoming the anticancer drug-resistance of cancer cells should be developed. However, the studies still remain in their early stage.